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Woolly Mammoth Revival

mammoth_steppe

Project goals

The ultimate goal of woolly mammoth revival is to produce new mammoths that are capable of repopulating the vast tracts of tundra and boreal forest in Eurasia and North America. The goal is not to make perfect copies of extinct woolly mammoths, but to focus on the mammoth adaptations needed for Asian elephants to live in the cold climate of the tundra. The milestones along the way range from developing elephant tissue cultures to genome editing and cloning.

The Harvard Woolly Mammoth Revival team has been working closely with Revive & Restore to study allele replacement (CRISPR genome editing) within elephant cells. We are interested in using genes from ancient mammoths to research evolutionary and ecological forces that impact speciation and extinction. Recent advances in DNA sequencing and genome editing are allowing functional experiments to test the links between genes and adaptations that may illuminate these areas of research, while simultaneously forming the groundwork for the de-extinction of mammoths.

Why bring back the woolly mammoth?

1) An Ecosystems approach to confront climate change

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Kolyma river lowland, 150 km away from the Arctic coast. On the Pleistocene Park pastures, horses, bison and musk ox have met again and maintain their pastures together.

The tundra and much of the taiga – the sometimes swampy coniferous forest of high northern latitudes – were once a grassland ecosystem known as the “mammoth steppe” which was home to abundant herds of antelope, deer, bovids, horses, and mammoths. At the end of the Pleistocene these herds vanished. The tundra that arose in the absence of these species is now contributing to human driven climate change. Without grasslands to insulate the tundra’s permafrost, the permafrost is melting, releasing greenhouse gases that have been trapped for tens and hundreds of thousands of years. The melting of the world’s permafrost is equivalent to burning all the world’s forests 2 ½ times.

The work of Dr. Sergey Zimov shows that tundra can readily be converted back to grasslands with the introduction of grazers even 10,000 years after their disappearance. The restored grassland not only insulates permafrost, it simultaneously sequesters atmospheric carbon.  The grassland also supports higher biodiversity.

Mammoths, like elephants in Africa today, were the engineers of grasslands keeping trees from growing onto the plains and dispersing large amounts of nutrients over immense distances. The mammoth is the keystone species to successfully restore populations of horse, bison, and other grazers.

2) Ancient DNA holds secrets that impact modern biology and medicine

A wealth of information exists in the genome of every species. Genomes are an encyclopedia of how to survive billions of years of catastrophes, epidemics, and changing conditions. Understanding the information locked in a genome is made possible by observing the living organism’s cells, tissues, body, and behavior. For extinct genomes such organismal interpretation is lost. Reanimation of genes in living cells allows us to discover the function of that prehistoric information in ways that studying genetic code alone can never provide. Mammoth hemoglobin, for example, may reveal information about mammalian blood useful to treating human diseases, and potentially the future of human space exploration (such as surviving cold environments); but the mutations that create mammoth hemoglobin need to be brought back to life for such discoveries to happen.

3) The future of large mammal conservation

The bioengineering, genome research, cellular resources, and reproductive techniques that will be developed to create mammoths directly enhance our understanding and ability to conserve elephant species.The bioengineering approaches tested may pave new ways to fight the ivory black market. For example, engineering biomarkers into tusks to track poaching, or more radically to alter tusks in a way that make them valueless to the ivory trade, which would allow male elephants to keep their large tusks – important indicators of good genes for mating. Cloning of mammoths, given their size, will push the limits of assisted reproductive capabilities to the benefit of crucial megafauna around the globe from severely endangered giraffe species to nearly extinct rhinoceros.

Work in progress

Building a mammoth out of an Asian elephant begins with three major adaptations:

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Mammoth_fat

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Blood oxygen release at low temperatures

Subcutaneous fat for
insulation, fasting

Thick hair protects
from the elements

Completed steps

The Harvard based team, led by Dr. George Church are currently using CRISPR genome engineering to copy/paste DNA from the mammoth genome into living elephant cell cultures (fibroblasts).

Mutations for mammoth hemoglobin and experimental mutations for fat and hair development have already been engineered into fibroblast cell lines using CRISPR editing technology.

Next steps:

1) These fibroblasts are being reprogrammed into induced pluripotent stem cells (iPSCs). Such stem cells are “immortal” in the lab, meaning there is no need for new cell cultures or harvesting from embryos.

2) The iPSC’s can be developed into multiple tissue types for studying the effects of mammoth mutations on the traits of cells. For example, the iPSCs will be developed into red blood cells. The oxygen carrying capacity of these blood cells can be tested under varying temperatures and stress conditions without ever producing an animal. Similar tests can be done for fat and hair growth.

mammoth_blood_transBlood cells

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Fat cells

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Hair cells

Further in the Future:

The complete genome sequence of the woolly mammoth is soon to be published. More research comparing the mammoth to the Asian elephant genome will identify new genes for more traits to test, such as reducing ear size to prevent heat loss.

Once studies of cell cultures produce promising results for the necessary adaptations to create a mammoth, the Mammoth Revivalists Team will begin cloning attempts. The nucleus of an Asian elephant egg cell will be removed and replaced with the nucleus of engineered mammoth cells. This fused embryo will then be developed in vitro and implanted into a living Asian elephant in captivity. After a two year pregnancy the world’s first new mammoth will be born. Dr. Church believes cloning attempts can begin by 2018.